PROJECT SUMMARY/ABSTRACT Maintenance dialysis is a form of potentially life-prolonging treatment for patients with end-stage renal disease (ESRD). However, dialysis also often demands significant lifestyle changes, and is associated with high rates of hospitalization and impaired physical and social function after initiation. For older patients with severe comorbidity, dialysis may not meaningfully lengthen survival and is associated with poorer quality-of-life as compared with more palliative approaches for ESRD, such as hospice. Decisions on dialysis are extraordinarily complex. In prior qualitative studies, patients with advanced chronic kidney disease (CKD) express significant uncertainty about whether dialysis is right for them. From the provider perspective, in similar qualitative interviews, nephrologists express frustration and hopelessness when caring for patients who are reluctant to take action to prepare for ESRD. Herein I propose a systematic research agenda using local and national study populations and a mixed-methods approach with quantitative and qualitative research techniques to investigate the potential mediators of patients' decisional uncertainty regarding treatment of ESRD and how this uncertainty may impact subsequent treatment practices and outcomes for ESRD. In Aim 1, I will leverage the comprehensive national electronic medical record of the Veterans Health Administration (VA) to perform an in-depth chart review and content analysis of documented patient-provider discussions on treatment of ESRD for a national cohort of patients with advanced CKD to determine the characteristics of these discussions that are associated with patients' uncertainty about these treatment decisions. The medical chart serves as an important record of healthcare interactions, accountability and communication, and provides a unique vantage point to examine treatment discussions as they unfold in clinical context. I will use novel text search software that I developed in my preliminary work to conduct a detailed review of each patient's medical record. The findings of this work will provide new insights into how to approach patient-provider discussions in order to better support patients with decisional uncertainty. For Aim 2, I will evaluate the burden of decisional uncertainty regarding treatment of ESRD in a diverse Seattle-based cohort of patients with advanced CKD using validated instruments measuring decisional uncertainty. I will test the association of these measures with prospectively collected information on conditions of dialysis initiation and utilization of palliative and hospice care to elucidate how addressing patients' uncertainty might improve treatment practices and outcomes for ESRD. For Aim 3, I will serially interview patient-nephrologist dyads over the course of advanced CKD to determine their perceived barriers to and facilitators of the decision-making process regarding treatment of ESRD, recognizing that decisions unfold and can change over time. The findings of this work will provide the basis for future interventions that enhance patients' readiness to face treatment decisions about ESRD and that are tailored to the distinct needs of patients and providers.